Green and blue coronavirus cells under magnification intertwined with DNA cell structure
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A recent University of Michigan study suggests a patient’s breath might be used to discern COVID-19, even variants, from non-COVID respiratory diseases.

The group used portable gas chromatography (GC) to examine breath samples collected during the pandemic’s Delta and Omicron surges (from April 2021 to May 2022.) Patients were diagnosed using reverse transcriptase polymerase chain reaction (RT-PCR).

They were able to distinguish Omicron, Delta, and non-COVID illness, between patients. The sensitivity of their testing was 89.4%, specificity was 91.0%, and accuracy was 90.2%.  Rates which, they note, are close to that of RT-PCR tests (the gold standard) and better than many rapid antigen tests. COVID testing is fraught with uncertainty, especially when variants are involved.

The team’s results, were published recently in JAMA Network Open. Besides showing that the GC technology could diagnose COVID-19 with a high level of accuracy, they also determined that the volatile organic compounds (VOCs) contained in the breath of patients with Omicron differed from those in patients with Delta and earlier variants.

“Exhaled breath contains hundreds of VOCs, which the body produces in response to infection and inflammation,” said principal investigator and study author Xudong (Sherman) Fan, PhD, professor of biomedical engineering and associate director of the Weil Institute.

He added that, “Early in the pandemic, we used GC technology to discover and define sets of VOCs for detecting COVID-19. However, we needed to gain a better understanding of how dynamically emerging variants impact this technology.”

They used a novel point-of-care GC device developed by Fan and the team, in combination with a biomarker discovery algorithm ,and data analysis platform developed at the College of Engineering and the Weil Institute.

The investigators first defined four sets of VOCs that were able to distinguish between COVID-19 (from 2021) and non-COVID illness with a sensitivity of 92.7%, a specificity of 95.5% ,and an accuracy of 94.7%. However, when the team applied the same VOCs in a setting of presumed Omicron, sensitivity decreased to 60.4%.

“We already knew clinically that different strains of SARS-CoV-2 can act quite differently,” said study co-author Robert Dickson, MD, deputy director of the Weil Institute. “This decrease in performance supports our suspicion that their effects on lung biology are quite different as well.”

The team then conducted a diagnostic study of 167 adult patients in the Michigan Medicine ICUs and emergency department. They collected 205 breath samples from symptomatic and asymptomatic patients in three cohorts:

  • Patients with COVID-19 who were recruited and were assumed to be infected by the Delta or earlier variants.
  • Patients with COVID-19 who were assumed to be infected by the Omicron variant.
  • Patients who were COVID-19 negative at the time of breath analysis, as well as patients who were previously COVID-19 positive but had recovered.

Based on their findings, the team hypothesized that it could be possible to use breath analysis to distinguish between COVID variants. They undertook additional biomarker searches and defined new VOCs for this next step, which culminated with their current publication.

Co-author Kevin Ward, MD, said, “This work suggests that breath analysis using point-of-care GC may be a promising method for detecting COVID-19 and similar diseases that result in VOC production. However, as we are seeing with other detection and testing methods, the emergence of viral variants continues to pose challenges.” Ward is executive director of the Weil Institute.

The team notes that further analysis will be needed to use breath analysis to improve the diagnosis and care of patients.

The portable GC technology has been licensed for commercialization from the University of Michigan by the company Blu Biotech.

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